GRIN1A/A0002

Grin2a (glutamate receptor, ionotropic, NMDA2A (epsilon 1)) also known as NR2A, is a type of NR2 subunit of the transmembrane N-methyl-D-aspartate (NMDA) receptor.

GRIN2A (glutamate receptor, ionotropic, NMDA2A epsilon 1), also known as NR2A or A0002, is a subunit of the transmembrane N-methyl-D-aspartate (NMDA) receptor, an important glutamate-gated ion channel expressed mostly in neurons. Knock-out of GRIN2A in mice results in decreased hippocampal long-term potentiation (LTP) and impaired learning and memory. GRIN2A is exclusively expressed postnatally and throughout the forebrain. It is highly expressed in the hippocampus and tends to be localized synaptically. Activity of GRIN2A has therefore been implicated in neuronal survival through the promotion of cyclic adenosine monophosphate (cAMP) response element binding (CREB)-dependent gene expression, and the inhibition of excitotoxicity. NMDA receptors are thought be tetrameric, composed of two NR1 subunits and two NR2 subunits. There are four NR2 subunits in vertebrates (GRIN2A-D) that show differential spatiotemporal expression patterns. GRIN2A is composed of an extracellular ligand-binding domain, transmembrane domains, and an intracellular C-terminal domain. The GRIN2A intracellular domain is over 600 amino acids long and contains numerous protein-protein interaction sites and phosphorylation sites. The PDZ binding domain at the C-terminus of NR2A is known to bind PSD95, PSD93, and SAP102. The structure of the GRIN2A intracellular tail is predicted to be unfolded and disordered. GRIN2A displays significantly higher rates of protein evolution in primates than in rodents, implicating GRIN2A in the evolution of the primate nervous system. Knock-in mice, where the intracellular domain of GRIN2A was specifically deleted, showed electrophysiological and behavioral phenotypes identical to the knock-out mice, demonstrating the importance of the intracellular domain for NMDA receptor function. GRIN2A polymorphisms are associated with schizophrenia and attention deficit/hyperactivity disorder (ADHD).